Apixaban is an active pharmaceutical ingredient used as anticoagulant for the treatment of venous thromboembolic events. Moreover it has also shown promise in treating acute coronary syndrome (ACS), cerebrovascular ischemia and cancer.
Apixaban having the following chemical formula (I):

has chemical name, 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5-dihydropyrazolo[5,4-c]pyridine-3-carboxamide and CAS RN 503612-47-3.
Several methods for the preparation of Apixaban have been described.
In particular, WO2007/001385 discloses a synthesis on multi-Kilos scale.
Specifically, WO2007/001385 discloses, in the example 6, a process for the preparation of Apixaban by amidation reaction on 10 Kg scale of the Apixaban ethyl ester according to the following reaction scheme:

According to said procedure, using anhydrous ammonia in propylene glycol and performing the reaction for at least 12 hours at 90° C., Apixaban was obtained with 94.6% of isolated molar yield.
Synthetic Communications, 43, 72-79, 2013 Jian'an Jing and YafeiJi discloses a cost-effective synthetic strategy to Apixaban as outlined in the scheme 3 at pag. 74 of said publication.
Another method for the preparation of Apixaban is disclosed in WO 03/049681; in particular, in the examples from 54 to 56, is described the route of synthesis for preparing said active pharmaceutical ingredient, starting from compound 10, an intermediate of Apixaban. Specifically in the example 54 in the last section of Part B., 3-Morpholin-4-yl-1-[4-(2-oxo-piperidin-1-yl)-phenyl]-5,6-dihydro-1H-pyridin-2-one (63) is produced by means of a mixture of ammonium hydroxide solution and EtOAc; finally the compound 63 is obtained after a purification by flash column chromatography. Instead, in the Part A of the same example is prepared a different compound, called copper (I), a catalyst, by means of a filtration and following washing with ethanol and then diethyl ether. The obtained copper (I) catalyses the reaction to produce the compound 63, therefore the above mentioned filtration and washing with ethanol and then diethyl ether are not carried out to produce the compound 63, but just to remove copper (I).
A further method to obtain an intermediate of Apixaban is disclosed in CN104030972. In particular in the example 1 is disclosed the process to obtain the compound (I), i.e. an intermediate of Apixaban. Specifically in the step (3) said compound is obtained by means of the addition of water followed by filtration; finally the compound (I) is produced with yield 74.0% and purity higher than 98.5%.
During our laboratory experimentation, it was surprisingly found that many routes of synthesis disclosed in the literature for the preparation of Apixaban provide product contaminated by impurities having high molecular weight.
The presence of said high molecular impurities, especially in amounts higher than 0.10%, is not acceptable in a pharmaceutical active substance such as Apixaban.